SRF binding to SRE in the rat heart: influence of age.
One important promoter element at the 5' end of the c-fos gene is the serum response element (SRE). SRE is the site of attachment of the 67-kDa protein serum response factor (SRF) and several accessory proteins (Elk1, SAP1, SAP2/NET), termed the ternary complex factors. The binding of SRF to SRE plays an integral role in c-fos transcription and may occur independently of the association of the ternary complex factors. In the current study, we found that SRF protein expression was increased in the hearts of the old vs young adult rats in the basal condition. The hearts of old rats may have posttranslationally modified SRF proteins that are different compared to that of the young adults. The SRF increase was present both in the cytoplasm as well as in the nucleus in the old hearts. To test whether SRF protein levels in response to acute stress might be altered with age, we studied hearts of young adult and old rats during myocardial infarction. The young adult rat hearts responded to acute ischemic stress with an increase in both p62 and p67 SRF. The hearts of the old rats, however, did not exhibit a significant change in SRF protein expression. These findings demonstrate qualitative as well as quantitative age differences in SRF protein levels, both at baseline and following stimulation. The reduced SRF expression in response to acute cardiac ischemic stress in the old rats might contribute to the observed age-related decrease in the induction of immediate early genes such as c-fos in the heart.
Lu
X G
XG
Gerontology Division, Beth Israel Deaconess Medical Center, New York, New York, USA.
Azhar
G
G
Liu
L
L
Tsou
H
H
Wei
J Y
JY
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005656:Fungal Proteins; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000235:genetics*; D007124:Immunoenzyme Techniques; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D050783:Proto-Oncogene Proteins c-ets; D051381:Rats; D011916:Rats, Inbred F344; D029702:Schizosaccharomyces pombe Proteins; D026362:Serum Response Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C086924:Elk3 protein, mouse; D005656:Fungal Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C085981:Sap1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida